Nicastrin、N1ICD及hes1蛋白在小鼠肝脏及肝癌组织中的表达

doi:10.3969/j.issn.1006-5725.2024.06.007

Abstract

Abstract:

Objective To detecting the expression of nicastrin， N1ICD and hes1 proteins in normal liver tissues and liver cancer tissues of C57BL/6 mice. Methods Twelve 6-week-old male C57BL/6 mice were randomly equally divided into the control group and model group. In the model group， the in situ liver cancer model was established with injection of Hepa1-6 cells into the liver， and the control group was treated with injection of the same amount of normal saline. Liver cancer was verified by HE staining. The expression of nicastrin， N1ICD and hes1 proteins in the normal and cancerous liver tissues was detected by IHC and Western blot. Results IHC results showed that nicastrin， N1ICD and hes1 proteins were localized in the hepatic sinusoidal endothelial cells in the normal hepatocytes， but not expressed in the hepatocytes. The model group showed higher expression of nicastrin protein but lower expression of N1ICD and hes1 protein in the cancer cells compared with the control group. Conclusion NCSTN gene may play a carcinogenic role in mouse hepatocellular carcinoma， while notch1 and hes1 may play a carcinostasis role in the carcinoma.

Key words: NCSTN, notch1, hes1, hepatocellular carcinoma, hepa1-6, mouse

CLC Number:

R735.7

Lu YAN,Tianwei SHI. Expression of nicastrin， N1ICD and hes1 proteins in normal and cancerous liver tissues of mice[J]. The Journal of Practical Medicine, 2024, 40(6): 768-772.

Figures/Tables 4

References 30

1	NISHIMORI N， HAYAMA K， KIMURA K， et al. A Novel NCSTN Gene Mutation in a Japanese Family with Hidradenitis Suppurativa［J］. Acta Derm Venereol， 2020， 100（17）：adv00283.
2	HESSAM S， GAMBICHLER T， SKRYGAN M， et al. Increased expression profile of NCSTN， Notch and PI3K/AKT3 in hidradenitis suppurativa［J］. J Eur Acad Dermatol Venereol， 2021， 35（1）：203-210. doi:10.1111/jdv.16962 doi: 10.1111/jdv.16962
3	LECHUGA G C， NAPOLEAO-PEGO P， GOMES L R， et al. Nicastrin-Like， a Novel Transmembrane Protein from Trypanosoma cruzi Associated to the Flagellar Pocket［J］. Microorganisms， 2021， 9（8）：1750. doi:10.3390/microorganisms9081750 doi: 10.3390/microorganisms9081750
4	URBAN S. Nicastrin guards Alzheimer's gate［J］. Proc Natl Acad Sci U S A， 2016， 113（5）：1112-1114. doi:10.1073/pnas.1524151113 doi: 10.1073/pnas.1524151113
5	HITZENBERGER M， GOTZ A， MENIG S， et al. The dynamics of γ-secretase and its substrates［J］. Semin Cell Dev Biol， 2020， 105：86-101. doi:10.1016/j.semcdb.2020.04.008 doi: 10.1016/j.semcdb.2020.04.008
6	ZHOU B， LIN W， LONG Y， et al. Notch signaling pathway： architecture， disease， and therapeutics［J］. Signal Transduct Target Ther， 2022， 7（1）：95. doi:10.1038/s41392-022-00934-y doi: 10.1038/s41392-022-00934-y
7	SPRINZAK D， BLACKLOW S C. Biophysics of Notch Signaling［J］. Annu Rev Biophys， 2021， 50：157-189. doi:10.1146/annurev-biophys-101920-082204 doi: 10.1146/annurev-biophys-101920-082204
8	ZHU C， HO Y J， SALOMAO M A， et al. Notch activity characterizes a common hepatocellular carcinoma subtype with unique molecular and clinicopathologic features［J］. J Hepatol， 2021， 74（3）：613-626. doi:10.1016/j.jhep.2020.09.032 doi: 10.1016/j.jhep.2020.09.032
9	QI R， AN H， YU Y， et al. Notch1 signaling inhibits growth of human hepatocellular carcinoma through induction of cell cycle arrest and apoptosis［J］. Cancer Res， 2003， 63（23）：8323-8329.
10	胡娜，宋毅，来卫东，等. Notch1、Jagged1在肝细胞癌组织中的表达及临床意义［J］. 中国医药导报，2013，10（19）：4-7. doi:10.3969/j.issn.1673-7210.2013.19.002 doi: 10.3969/j.issn.1673-7210.2013.19.002
11	潘振奎，梁忆波，冉雯雯，等. 肝细胞癌中Notch1和Notch3的表达及其临床意义［J］. 临床肿瘤学杂志，2014，19（1）：42-45.
12	HANY H， SHALABY A， AL K W， et al. Evaluation of the role of Notch1 expression in hepatic carcinogenesis with clinico-pathological correlation［J］. Pathology， 2018， 50（7）：730-736. doi:10.1016/j.pathol.2018.08.007 doi: 10.1016/j.pathol.2018.08.007
13	CHEN F， YU G， ARAWAKA S， et al. Nicastrin binds to membrane-tethered Notch［J］. Nat Cell Biol， 2001， 3（8）：751-754. doi:10.1038/35087069 doi: 10.1038/35087069
14	WOO H G， PARK E S， LEE J S， et al. Identification of potential driver genes in human liver carcinoma by genomewide screening［J］. Cancer Res， 2009， 69（9）：4059-4066. doi:10.1158/0008-5472.can-09-0164 doi: 10.1158/0008-5472.can-09-0164
15	WANG X， WANG X， XU Y， et al. Effect of nicastrin on hepatocellular carcinoma proliferation and apoptosis through PI3K/AKT signalling pathway modulation［J］. Cancer Cell Int， 2020，20：91. doi:10.1186/s12935-020-01172-4 doi: 10.1186/s12935-020-01172-4
16	GIOVANNINI C， GRAMANTIERI L， MINGUZZI M， et al. CDKN1C/P57 is regulated by the Notch target gene Hes1 and induces senescence in human hepatocellular carcinoma［J］. Am J Pathol， 2012， 181（2）：413-422. doi:10.1016/j.ajpath.2012.04.019 doi: 10.1016/j.ajpath.2012.04.019
17	吴艳，林丹丹，包光明. 两种方法建立小鼠原位肝癌模型的比较［J］. 医药前沿，2013（14）：382-383. doi:10.3969/j.issn.2095-1752.2013.14.463 doi: 10.3969/j.issn.2095-1752.2013.14.463
18	LLOVET J M， KELLEY R K， VILLANUEVA A， et al. Hepatocellular carcinoma［J］. Nat Rev Dis Primers， 2021， 7（1）：6. doi:10.1038/s41572-020-00240-3 doi: 10.1038/s41572-020-00240-3
19	张晓坤，司徒瑞儒. 甲胎蛋白、甲胎蛋白异质体3比率、高尔基体蛋白73联合检测在原发性肝癌诊断中的价值［J］. 实用医学杂志，2021，37（8）：1068-1071.
20	LI H， LAN T， XU L， et al. NCSTN promotes hepatocellular carcinoma cell growth and metastasis via beta-catenin activation in a Notch1/AKT dependent manner［J］. J Exp Clin Cancer Res， 2020， 39（1）：128. doi:10.1186/s13046-020-01638-3 doi: 10.1186/s13046-020-01638-3
21	GHARAIBEH L， ELMADANY N， ALWOSAIBAI K， et al. Notch1 in Cancer Therapy： Possible Clinical Implications and Challenges［J］. Mol Pharmacol， 2020， 98（5）：559-576. doi:10.1124/molpharm.120.000006 doi: 10.1124/molpharm.120.000006
22	王卫东，陈小伍，吴志强，等. 肝细胞癌组织中Notch1和Jagged1的表达及意义［J］. 广东医学，2015，36（5）：763-766.
23	JUE C， LIN C， ZHISHENG Z， et al. Notch1 promotes vasculogenic mimicry in hepatocellular carcinoma by inducing EMT signaling［J］. Oncotarget， 2017， 8（2）：2501-2513. doi:10.18632/oncotarget.12388 doi: 10.18632/oncotarget.12388
24	WU C X， XU A， ZHANG C C， et al. Notch Inhibitor PF-03084014 Inhibits Hepatocellular Carcinoma Growth and Metastasis via Suppression of Cancer Stemness due to Reduced Activation of Notch1-Stat3［J］. Mol Cancer Ther， 2017， 16（8）：1531-1543. doi:10.1158/1535-7163.mct-17-0001 doi: 10.1158/1535-7163.mct-17-0001
25	SUI C， ZHUANG C， SUN D， et al. Notch1 regulates the JNK signaling pathway and increases apoptosis in hepatocellular carcinoma［J］. Oncotarget， 2017， 8（28）：45837-45847. doi:10.18632/oncotarget.17434 doi: 10.18632/oncotarget.17434
26	RANI A， GREENLAW R， SMITH R A， et al. HES1 in immunity and cancer［J］. Cytokine Growth Factor Rev， 2016， 30：113-117. doi:10.1016/j.cytogfr.2016.03.010 doi: 10.1016/j.cytogfr.2016.03.010
27	CHEN Z， ZUO X， PU L， et al. Hypomethylation-mediated activation of cancer/testis antigen KK-LC-1 facilitates hepatocellular carcinoma progression through activating the Notch1/Hes1 signalling［J］. Cell Prolif， 2019， 52（3）：e12581. doi:10.1111/cpr.12581 doi: 10.1111/cpr.12581
28	冯娜. Hes1基因与原发性肝癌发生相关性的体内外实验研究［D］.上海：第二军医大学，2013.
29	XIANG Z， MIAO Q， ZHANG J， et al. AB4 inhibits Notch signaling and promotes cancer cell apoptosis in liver cancer［J］. Oncol Rep， 2021， 45（6）：112. doi:10.3892/or.2021.8063 doi: 10.3892/or.2021.8063
30	ZHANG Y， YI B， ZHOU X， et al. Overexpression Of ERbeta Participates In The Progression Of Liver Cancer Via Inhibiting The Notch Signaling Pathway［J］. Onco Targets Ther， 2019， 12：8715-8724. doi:10.2147/ott.s218158 doi: 10.2147/ott.s218158

[1]	Li XIAO,Shumin LUO,Fang XU,Pengpeng LU,Enhong XING,Weihua. LI. Effect of culture time on immune⁃related membrane proteins of mouse dendritic cells and their exosomes [J]. The Journal of Practical Medicine, 2024, 40(7): 941-947.
[2]	Fazhu FEI,Jiajun LU,Shuai ZHANG,Hao LI,Bin REN. Clinical application progress of immunization and targeted therapy for Hepatocellular Carcinoma in special populations [J]. The Journal of Practical Medicine, 2024, 40(6): 738-742.
[3]	Zhipeng WU,Yuqin ZHANG,Minggang WANG,Rongzhen ZHANG,Dewen. MAO. Expression and biological function of TRP signaling pathway in hepatocellular carcinoma [J]. The Journal of Practical Medicine, 2024, 40(6): 743-747.
[4]	Yuxin CHENG,Liang LIU,Shiyu DONG,Shengchao LI,Meng ZHANG. Research advances in exosomal proteins， mRNA and non⁃coding RNA regulation of Hepatocellular Carcinoma [J]. The Journal of Practical Medicine, 2024, 40(6): 748-755.
[5]	Junhong XU,Hongbing YAO,Xueyao WANG,Wei GUO,Caijin LU,Jiaxing WU,Jianhui JIANG,Dongkang ZHAO. Clinical efficacy of FOLFOX⁃HAIC combined with lenvatinib and PD⁃1 inhibitor in the treatment of intermediate and advanced Hepatocellular Carcinoma [J]. The Journal of Practical Medicine, 2024, 40(6): 762-767.
[6]	Li XU,Shanshan HU,Haiming. ZHAO. LncRNA GNAS⁃AS1 participates in the proliferation and migration of gastric cancer cells by regulating the miR⁃449a/Notch1 axis [J]. The Journal of Practical Medicine, 2024, 40(4): 483-489.
[7]	Yi WANG,Shuo HE,Siyun YANG,Jun. ZHANG. In vitro study of 5⁃FU combined with rhCYGB in treating hypoxia⁃induced chemotherapy resistance of hepatocellular carcinoma [J]. The Journal of Practical Medicine, 2024, 40(22): 3146-3154.
[8]	Hua WANG,Yue HEI,Miao SUN,Yanchuang SUN,Juan HAN,Juanhua. SUN. Efficacy of bevacizumab combined with raltitrexed in the treatment of unresectable hepatocellular carcinoma and its influence on adverse reactions and survival rate [J]. The Journal of Practical Medicine, 2024, 40(21): 3061-3066.
[9]	WU Linghong, ZHOU Min, LU Yao, ZHU Guangwei.. Value of neutrophil/lymphocyte ratio and its variation value in predicting risk of acute liver function deteri⁃ oration after interventional treatment of hepatocellular carcinoma [J]. The Journal of Practical Medicine, 2023, 39(6): 713-719.
[10]	ZHAN Yi, NI Caifang, ZHONG Binyan, TIAN Pengcheng.. Research advances of ALBI grade for liver function assessment and prognosis stratification [J]. The Journal of Practical Medicine, 2023, 39(3): 381-385.
[11]	Yan LIU,Donghua ZHANG,Yuqian HUANG,Youshun LIU,Ji. HUANG. Inhibitory effect of pristimerin on diethylnitrosamine⁃induced hepatocellular carcinoma in rats by regulating ROS/ASK1/JNK signal pathway [J]. The Journal of Practical Medicine, 2023, 39(20): 2597-2602.
[12]	LI Feiyan , ZHANG Riyun, WANG Na, WANG Minggang, MAO Dewen. . The role of phospholipase A2 in the development of Hepatocellular carcinoma [J]. The Journal of Practical Medicine, 2023, 39(15): 1857-1861.
[13]	WANG Siyi , LU Jianing, HUANG Qinghui. . Evaluation of depression in a mouse model of smog⁃induced chronic obstructive pulmonary disease [J]. The Journal of Practical Medicine, 2023, 39(15): 1862-1868.
[14]	LIU Wenying, QUE Yuan, OUYANG Zaixing, ZHU Jianhua, WU Liming, TAN Yong, SONG Hao, ZHU Yuzhen, HUANG Congyun.. Clinical application value of terminal branches portal vein embolization and multimode imaging technolo⁃ gy in precise hepatectomy of huge hepatocellular carcinoma [J]. The Journal of Practical Medicine, 2023, 39(12): 1546-1550.
[15]	WEN Jing, HE Rong, ZHANG Hongwei, XIONG Qiqiu, JIA Zhe, ZHANG Ke. . Evaluation of safety and efficacy of simultaneous surgery for portal hypertension with hepatocellular carci⁃ noma [J]. The Journal of Practical Medicine, 2023, 39(11): 1416-1421.

Expression of nicastrin， N1ICD and hes1 proteins in normal and cancerous liver tissues of mice

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 4

References 30

Related Articles 15

Recommended Articles

Metrics

Comments